The physiological function and the mode of regulation of the transglutaminases, which catalyze the formation of covalent cross-links between protein molecules, are being studied. Three distinct classes of these enzymes, previously defined are characterized in this laboratory, participate in stabilization of the fibrinclot and in cross-linking of other proteins. The ameobocytes of Limulus Polyphemus show cellular properties similar to human platelets in their ability to adhere, to aggregate, and to release cellular transglutaminase for formation of a matrix of protein polymers at the site of injury. Thus, this system was chosen to serve as a model to study the complex would healing process. Of particular interest are the roles of the individual transglutaminases in the stabilization of the cellular membrane of ovum after sperm penetration and seminal plasma coagulation during fertilization. The regulation of the level of protransglutaminase in blood plasma by its binding protein, and the biosynthesis of each in the whole animal are also under investigation.